Refresher course for primary exam May 2008

ENDOCRINE PHYSIOLOGY - VIVA/ESSAY QUESTIONS

1. Outline the synthesis and functions of thyroid hormones and how their
secretion regulated.

2. a) State and briefly explain the physiological functions of calcium.

b) Describe the regulation of plasma calcium.

3. Discuss briefly the functions of aldosterone and the role of renin-

angiotensin system in the regulation of its secretion.

4. Outline the factors which are involved in the control of blood glucose
levels.

5. List the effects of insulin in various tissues.

1. Outline the synthesis and functions of thyroid hormones and how their secretion
regulated.

Sample answers:
a) Thyroid hormone synthesis and regulation
- Iodide trapped by follicular epithelium
- transported into colloid against conc. gradient (energy dependent)
- iodide then oxidized to iodine
- tyrosine residues within thyroglobulin are iodinated to form monoiodotyrosine (MIT)
and diiodotyrosine (DIT)
- MIT + DIT = T3 , DIT + DIT = T4
- thyroid peroxidase enzyme catalyst this series of reactions
- produce 80% T4 and 20% T3
- exocytosis from the epithelium when needed
- bind to TBG/TBPA/Alb in plasma (99.98% T4 is bound)
- synthesis/release stimulated by TSH
- 5 stages: absorption, trapping, organification, coupling, secretion
- TSH stim. stage 2-5, thyroid gland vascularity, increase thyroglobulin.
Physiologic effects of thyroid hormones:

Target tissues Effect Mechanisms

Increase number and affinity B-
Chronotropic
adren. rec.
Enhance response to
Heart
cathecolamines.
Inotropic
Increase proportion of alpha
myosin heavy chain
Adipose tissue Catabolic Stim. lipolysis
Muscle Catabolic Incr. protein breakdown
Promote normal growth and
Bone Developmental
skeletal dev.
Nervous system Developmental Promote normal brain dev.
Gut Metabolic Incr. rate of CHO absorption
Lipoprotein Metabolic Stim formation of LDL rec
Stim O2 consumption by
Other Calorigenic metabolic active tissues.
Incr. metabolic rate.

Functions of thyroid hormones

i. Metabolic effects –↑of BMR, ↑ O2 consumption, heat production
- ↑of CHO metabolism
- ↑catabolism of FFA
- ↑ protein synthesis and breakdown
ii. Systemic effects – stim. of HR
- ↑ ventilation
- ↑ GIT motility/secretion
- ↑ CNS activity
iii. developmental effects – skeletal growth in childhood
- promotional of normal brain
2. a) State and briefly explain the physiological functions of calcium.
b) Describe the regulation of plasma calcium.

a) Functions of Ca

i. Cytoplasm - excitation-contraction coupling in all muscle

- excitation-secretion coupling – endocrine/exocrine fn
- enzyme cofactor
- regulation of mitotic activity

ii. Cell membrane - excitability of nerve and muscle membrane

- automaticity of smooth muscle/SA & AV nodes
- neurotransmitter release at NMJ
- neurohormonal release & activity eg. alpha adr, Ach, ADH, oxytocin

iii. Extracellular - coagulation cascade I, II, VII, IX, X (haemostasis)

- complement cascade
- WBC chemotaxis
- bone & teeth formation (Ca hydroxyapetite)

b) Regulation of plasma Ca

- [Ca] 2.20-2.55 mmol/l

- 50% ionized, 40% bound, 10% non-ionised complex with citrate/PO4
- most important influence on protein binding is plasma pH
- alkalosis ⇒ ↑ binding Ca due to exposure of more anionic sites ⇒ ↓ ionized Ca
- acidosis ⇒ ↓ binding Ca ⇒ ↑ ionized Ca
- mainly 2 hormones ie PTH, Vit D
- PTH - 4 parathyroid glands, secreted by chief cells
- a polypeptide, t1/2 10 min

- ↑ Ca release from bone (incr bone resorption)

- ↑ reabsorption of Ca in renal tubules
- ↑ urinary PO4 excretion
- ↑ production of Vit D3 (indirect effect)

- Vit D - 7-dehydrocholestrol + UV light (skin) ⇒ vit D3 (cholecalciferol)

- diet (vit D2)
- vit D3 ⇒ 25-D3 ⇒ 1,25 D3
(liver) (kidney)
- stimulated by – PTH, low Ca/PO4
- ↑ uptake Ca/ PO4 from gut
- ↑ reabsp. Ca/ PO4 from renal tubules
- bone resorption/promotes mineralization

- Calcitonin – C cells of the thyroid (parafollicular cells)

- lower Ca during episode of hyperCa
- acts on bone to reduce rate of release of Ca (inhi bone resorption)
- no significant role in normal Ca haemostasis.

3. Discuss briefly the functions of aldosterone and the control of its secretion.

- 95% of mineralocorticoid activity

- secretion regulated by:
i. RAAS
- renin released by JG cells : - ↓ pressure in afferent arteriole
- ↓ flow in distal tubule detected by macula densa
- ↑ sympathetic activity

AT ⇒ ATI ⇒ ATII ⇒ ATIII (40% pressor effect)

renin ACE angiotensinogenase

- ATII effects: - vasoconstriction (↑MAP, ↑RPP, ↓ renin)

- thirst & stim ADH
- Na and H2O excretion
- stim aldosterone release
- ↓ sensitivity of baroreceptor reflex ⇒ potentiate the pressor effect
- ↑ vasopressin/ACTH release

ii. ↑ [K] (much less changes in [Na])

iii. ACTH – necessary but not important in normal regulation

Functions of aldosterone:
i. control of electrolyte/fluid content in the ECF
- active reabsorption of Na in distal tubule
- secretion of K (main negative feedback)
- secretion of H (minimal)

4. Outline the factors which are involved in the control of blood glucose
levels.

- normal 4-7 mmol/L

- determined by balance between amount entering the blood and the amount leaving it.
- main determinants: - dietary intake, renal loss (threshold 10mmol/L)
- rate of entry into cells of muscle/adipose (insulin dependent)
- utilization by non-insulin dependent organs eg nerves, rbcs,
exercising muscle etc
- glycostatic activity of liver
- after meal – glucose level ↑ ⇒ insulin release ⇒ entry of glucose into liver (glycogen,
oxidation), muscle (glycogen), adipose (glycerol)
- fasting - glucose level ↓ ⇒ insulin ↓ glucagon ↑ ⇒ ↑ glycogenolysis, gluconeogenesis
in the liver ⇒ release of glucose ↑

Other neural-hormonal factors:

Cortisol – permissive role, required for glucagons/adrenaline activity
Catecholamines – ↑ hepatic glycogenolysis, lipolysis
GH – inhibit uptake of glucose by muscle cells, ↑ glucose release by liver
Thyroid hormones – ↑ GIT absorption, ↓ glycogen synthesis
Oestrogen/progesterone/HPL – insulin resistance
Somatostatin – inhibit release of insulin/glucagons
Sympathetic – by hypoglycaemia
Hypothalamus – appetite centre

5. List the effects of insulin in various tissues.

- anabolic hormone, polypeptide with 2 chains linked by disulphide bond

- t1/2 5 min, internalized after binding to rec.
- 80% degraded by liver and kidney

- Principal actions of insulin:

i. rapid (seconds) - ↑ transport of glucose, amino acids and K into insulin
sensitive cells
ii. intermediate (min) - stim of protein synthesis
- inhi og protein degradation
- activation of glycolytic enzymes and glycogen synthase
- inhi of phosphorylase and gluconeogenic enzymes

iii. delayed (hrs) - ↑ in mRNA for lipogenic and other enzymes

Effect of insulin in various tissues

↑ glucose entry
↑ fatty acid synthesis
↑ glycerol phosphate synthesis
Adipose tissue ↑ triglyceride deposition
activation of lipoprotein lipase
inhibition of hormone sensitive lipase
↑ K uptake
↑ glucose entry
↑ glycogen synthesis
↑ amino acid uptake
↑ protein synthesis in ribosomes
Muscle ↓ protein catabolism
↓ release of gluconeogenic a.a
↑ ketone uptake
↑ K uptake
↓ ketogenesis
↑ protein synthesis
Liver ↑ lipid synthesis
↓ glucose output
General ↑ cell growth